Role of matrix metalloproteinases in the pathogenesis of idiopathic pulmonary fibrosis.
Role of matrix metalloproteinases in the pathogenesis of idiopathic pulmonary fibrosis.
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DOI：
10.1186/s12931-016-0343-6
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发表时间：
2016-03-04
影响因子：
5.8
通讯作者：
Selman M
中科院分区：
文献类型：
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作者：
Pardo A;Cabrera S;Maldonado M;Selman M
特发性肺纤维化（IPF）是一种原因不明的进行性和破坏性肺部疾病，预后非常差，没有有效的治疗方法。该疾病的特征在于肺泡上皮细胞的异常活化，其分泌参与成纤维细胞群体的扩增、其向肌成纤维细胞的分化以及引起肺结构丧失的细胞外基质的过度积累的多种介质。在过度产生的介质中有几种基质金属蛋白酶（MMP），它们可能通过各种机制改变肺微环境。因此，这些酶不仅可以降解细胞外基质的所有组分，而且它们还能够释放、切割和激活广泛的生长因子、细胞因子、趋化因子和细胞表面受体，影响许多细胞功能，包括粘附、增殖、分化、募集和迁移以及凋亡。因此，MMPs的表达失调可能对IPF发展中涉及的生物病理学机制产生深远影响。本文综述了目前和新出现的证据，关于基质金属蛋白酶在IPF以及小鼠肺纤维化模型的纤维化过程中的作用。
Idiopathic pulmonary fibrosis (IPF) is a progressive and devastating lung disorder of unknown origin, with very poor prognosis and no effective treatment. The disease is characterized by abnormal activation of alveolar epithelial cells, which secrete numerous mediators involved in the expansion of the fibroblast population, its differentiation to myofibroblasts, and in the exaggerated accumulation of extracellular matrix provoking the loss of lung architecture. Among the excessively produced mediators are several matrix metalloproteases (MMPs) which may contribute to modify the lung microenvironment by various mechanisms. Thus, these enzymes can not only degrade all the components of the extracellular matrix, but they are also able to release, cleave and activate a wide range of growth factors, cytokines, chemokines and cell surface receptors affecting numerous cell functions including adhesion, proliferation, differentiation, recruiting and transmigration, and apoptosis. Therefore, dysregulated expression of MMPs may have profound impact on the biopathological mechanisms implicated in the development of IPF. This review focuses on the current and emerging evidence regarding the role of MMPs on the fibrotic processes in IPF as well as in mouse models of lung fibrosis.